Progress report (final) of the OTKA T049492 project
N-methyl group of L-deprenyl was labeled using 14C. The 14C-labelled methyl group was used to trace its fate in the body. Generation of 14C-labelled formaldehyde was verified using TLC, HPLC, HPLC-MS and HPLC-MS-MS. One part of the generated formaldehyde was urinary eliminated, an another part took place in the methylation reaction of L-lysine giving 14C-labelled N-E-monomethyl lysine. The ratio of the 14C-labelled deprenil metabolites was: methamphetamine:p-hydroxy-methamphetamine:deprenylformaldehyde = 20:3:1:1. Only a minor part of formaldehyde was subjected to N-methylation of lysine.
Free lysine molecules were solely methylated, lysine residues of either peptides or proteins were not methylated by formaldehyde originated from deprenyl. N-methylation of lysine was not found under the effect of regular daily food, nor N-E-monomethyl lysine was detected under pathological conditions of blood vessels.
Special prodrugs are activated by O-deethylation. Metabolic O-ethyl to N-ethyl transfer was not indicated during our metabolic study of moexipril.
Alkyl-bridged quaternary amines (e.g. bis-pyridinium aldoximes) did not show metabolic N-dealkylation or alkyl transfer to another compound.